A gut-brain interaction controlling reward learning

控制奖励学习的肠脑相互作用

基本信息

批准号：
10677021
负责人：
William Matthew Howe
金额：
$ 35.47万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-05 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677021
关键词：
Adaptive Behaviors Address Anatomy Appetitive Behavior Behavior Behavioral Big Data Brain Calories Carbohydrates Cells Code Collaborations Consumption Corpus striatum structure Data Data Analyses Disease Dissociation Dopamine Dorsal Drug abuse Eating Event Fatty acid glycerol esters Fiber Food Foundations Functional Magnetic Resonance Imaging Future Goals Human Immunohistochemistry Individual Infusion procedures Knowledge Label Lead Learning Link Macronutrients Nutrition Measures Mediating Mental Depression Midbrain structure Modeling Modernization Monitor Motivation Mus Natural Selections Neurobiology Neurons Neurosciences Nucleus Accumbens Nutrient Obesity Optics Oral cavity Pathway interactions Peripheral Phenotype Photometry Play Population Proteins Psychological reinforcement Research Research Support Rewards Role Self Stimulation Shapes Signal Transduction Statistical Models Stimulus Substantia nigra structure Support System System Techniques Technology Testing Time Training Ventral Tegmental Area Viral Vector Work computational neuroscience design dopamine system experimental study genetic manipulation gut-brain axis human subject neural novel recruit reinforced behavior response stem theories translational potential

项目摘要

Project Summary/Abstract The functions and computations supported by changes in the activity of meso-striatal dopamine systems are some of the most heavily researched, and hotly debated, topics in modern neuroscience. Predominant theories propose that they support reinforcement learning by broadcasting prediction-error signals, encode stimulus salience, or generally motivate reward seeking by representing internal states. Furthermore, it is widely accepted that these systems have been shaped by natural selection to reinforce adaptive behaviors. Eating, or the pursuit of nutrients, is fundamental for survival, and previous work has demonstrated that striatal DA circuits are critical components of the neurobiological systems that support this behavior. Importantly, emerging research supports a model whereby midbrain DA populations receive signals from the gut about food content that modify their activity and contribute to food learning and motivation. However, the timescale over which these gut-derived signals modulate DA release, and how they interact with DA signals previously identified as critical for food reward learning and motivation, is largely unknown. Here, we propose to address these gaps in our knowledge by using state of the art techniques to 1) Identify the ensembles of neurons in midbrain dopamine populations that are recruited by post-ingestive signals to control food reward. 2) Characterize the ability of post-ingestive signals to modify reward learning via effects on dopamine release in subregions of the striatum. 3)Test the causal role of post-ingestive signals for dopamine control of food reward. To accomplish these aims, we have assembled a team including behavioral and systems neuroscientists with expertise in modern technologies for recording and manipulating genetically defined cell populations, translational neuroscientists with expertise in the neurobiology of appetitive behaviors, statisticians specializing in big-data analysis, as well as leaders in the field of computational neuroscience. Completion of these studies will provide an opportunity to integrate peripheral modulation of midbrain dopamine systems into current models of dopamine control of reward learning and motivation, and provide a foundation for future studies of peripheral-central dopamine contributions to multiple adaptive functions and disease states.

项目概要/摘要中纹状体多巴胺系统活动变化支持的功能和计算是现代神经科学中一些研究最深入、争论最激烈的主题。主流理论提出他们通过广播预测误差信号、编码刺激来支持强化学习显着性，或者通常通过代表内部状态来激发奖励寻求。此外，它被广泛接受这些系统是通过自然选择形成的，以加强适应性行为。吃，还是追求营养物质，是生存的基础，之前的工作已经证明纹状体 DA 回路至关重要支持这种行为的神经生物系统的组成部分。重要的是，新兴研究支持中脑 DA 群体从肠道接收有关食物含量的信号的模型，从而改变其活动并有助于食物学习和动机。然而，这些肠道来源的时间尺度信号调节 DA 释放，以及它们如何与先前确定对食品至关重要的 DA 信号相互作用奖励学习和动机，很大程度上是未知的。在这里，我们建议解决我们知识中的这些差距通过使用最先进的技术来 1) 识别中脑多巴胺群体中的神经元集合通过摄入后信号招募来控制食物奖励。 2) 表征摄入后的能力通过影响纹状体次区域多巴胺释放来改变奖励学习的信号。 3）检验因果关系摄入后信号对多巴胺控制食物奖励的作用。为了实现这些目标，我们有组建了一支由具有现代技术专业知识的行为和系统神经科学家组成的团队记录和操纵基因定义的细胞群，具有专业知识的转化神经科学家食欲行为的神经生物学、专门从事大数据分析的统计学家以及该领域的领导者计算神经科学领域。完成这些研究将提供整合的机会中脑多巴胺系统的外周调节进入当前奖励学习的多巴胺控制模型和动机，并为未来研究外周-中枢多巴胺的贡献奠定基础多种适应功能和疾病状态。